Abstract

Recently, "low dose and long term" erythromycin (EM) treatment has been reported as effective on chronic lower respiratory tract disease, including diffuse panbronchiolitis (DPB). However the effective mechanism of EM is still obscure. In this study, we investigated the effect of EM on intrapulmonary influx of neutrophils by intratracheal injection of lipopolysaccharide (LPS), and the following results were obtained. 1) The intrapulmonary influx of neutrophils was significantly suppressed (p less than 0.001) in mice intraperitoneally injected with EM at 5 mg per animal 2 hr before intratracheal injection of LPS (control group: 6.5 +/- 0.8 x 10(5) vs EM-treated group: 1.7 +/- 0.3 x 10(5)), but not 10 hr before lung challenge. This inhibition was observed at 6 hr after lung challenge, and became maximum with 84% suppression at 24 hr. 2) The intrapulmonary influx of neutrophils was not affected when EM was injected intraperitoneally daily for 3, 7, or 14 days, and lung challenge was performed 24 hr after the final administration of EM. 3) The number of neutrophils in the peripheral blood was not affected by EM. These results suggest that EM treatment impairs the capacity for pulmonary inflammation by reducing, at least in part, the migration of neutrophils to inflammatory sites.

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